During vertebrate cardiac morphogenesis, the definitivce pulmonary and systemic outflow structures are formed through division and reorganization of the embryonic truncus arteriosus. Classical descriptions of tissue interactions and cellular differentiation during truncal septation conflict with the results of recent study. The purpose of the proposed research is to test a new model of this critical morphogenetic event by examining the cytokinetics and ultrastructure of truncal septation in the normal chick and rat heart and its disruption following teratogenic treatment. The origins and fates of the several cell populations which participate in truncal septation will be charted quantitatively with a combination of morpholgical techniques including tissue marking, serial sectioning, and cell counting methods. Once these tissue movements have been described with the light microscope, we will examine the ultrastructural events which accompany the differentiation of individual structures within this region - the aorticopulmonary septum, the conus septum, the semilunar valves, and their attachments to the developing myocardium and arterial smooth muscle. The role of shifting mechanical stress in truncal morphogenesis will be assessed by analyzing changes in the distribution and orientation of intracellular and extracellular matrix fibers as septation proceeds. These indices of normal septation will be used as the basis for describing cellular level changes induced by teratogenic treatment with bromodeoxyuridine and theophylline. The cardiac outflow structures to be studied are directly involved in about one-third of the congenital cardiac defects found in human infants. The proposed research is designed to further the long-range objective of describing normal and experimentally altered truncal development in sufficient detail to understand and eventually prevent such malformations.